As reductionist biomedical science succeeds in elucidating ever more detail at the molecular level, a mathematical modeling framework will become increasingly important to cope with this explosion of data and to relate integrated whole organ function to underlying biophysically detailed mechanisms that exploit this molecular knowledge. The proposed research has two primary long term objectives. The first is to continue development of an extensible anatomically and biophysically based modeling framework that can be used to integrate the physiological, anatomical and medical knowledge of the gastrointestinal (GI) system. The second objective is to focus this integrative modeling framework on three major diseases of the GI tract that affect a significant number of people in the United States, namely intestinal ischemia, diabetic gastro paresis and irritable bowel syndrome (IBS). Prior research has shown that recordings of the magnetic field from gastrointestinal electrical activity using multichannel Superconducting QUantum Interference Device (SQUID) magnetometers provides a noninvasive and noncontact assessment of the physiological state of the GI smooth muscle. We will combine multichannel SQUID and cutaneous electrode measurements with anatomically based integrative computer models to investigate the inter- and intra-subject effects of intestinal ischemia, gastro paresis and IBS on GI electrical activity noninvasively. We hypothesize that the resulting integration of anatomical and physiological biophysical properties will serve as a basis for a more complete understanding of the gastrointestinal system and will aid in the detection and diagnosis and, ultimately, in the treatment of gastrointestinal disorders. This is necessarily a collaborative project that initially involves five main groups (the Living State Physics Group at Vanderbilt University, the Department of Surgery at Vanderbilt University, the Department of Physiology and Cell Biology, University of Nevada, the Enteric Neuroscience Program at Mayo Clinic and the Auckland Bioengineering Institute) and combines expertise in integrated biophysically based modeling with physiological, clinical and research expertise in the function of the gastrointestinal system PUBLIC HEALTH RELEVANCE: Currently there are no non-invasive diagnostic procedures for assessing many electrophysiological GI disorders despite their prevalence. This project aims to investigate the bioelectromagnetic fields associated with three common gastrointestinal conditions that affect a significant proportion of the population: intestinal ischemia, gastro paresis and irritable bowel syndrome. We aim to address significant gaps in our knowledge about each of these conditions and ultimately wish to develop a method to non-invasively determine underlying physiological and pathophysiological mechanisms of gastrointestinal electrical activity.